Methods: This retrospective chart review (n=298) examined the outcomes of pediatric patients who receivied ketorolac during ERCP compared to those who did not; ketorolac, was dosed using weight-based dosing (0.5 mg/kg/dose max 30 mg).
Most common indications for ERCP were choledocholithiasis, biliary stricture, and chronic/recurrent pancreatitis
Therapeutic ERCP: 91% of ketorolac group and 89% of non-ketorolac group; sphincterotomy was performed in 55% of both groups
Post-ERCP bleeding rates were not significantly different between ketorolac and non-ketorolac groups (0.6% vs 0%, P = 1)
PEP (post-ERCP pancreatitis) rates were not significantly different between the ketorolac and no ketorolac group 15/166 vs 17/132 (9% vs 13%, P = 0.29)
Patients who had cannulation and/or injection of the PD had significantly higher rates of PEP (23/140 (16%) vs 9/158 (6%), P < 0.003)
For high-risk pediatric patients with injection of contrast into and/or cannulation of the pancreatic duct, the rates of PEP were significantly lower for patients who received ketorolac (11% vs 25%, P = 0.035). In Table 2, the authors indicate that PEP in this high risk group occurred in 11/88 (12.5%) [mild discrepancy from abstract of 11%] of ketorolac group and 13/52 (25%)
It is possible that ketorolac (or other NSAIDs) in all patients may be beneficial but difficult to demonstrate without a larger cohort. In adults, “indomethacin reduces risk and severity of PEP in both high and average risk adults…and there is some evidence that NSAIDS given before ERCP may be more effective than those given later.” Thus, the authors state that use of ketorolac could be administered to all ERCP patients beforehand (w/o contraindication) or limited to the higher risk patients.
My take: In pediatric patients needing an ERCP, those with high-risk features (eg. injection of contrast into and/or cannulation of the pancreatic duct), use of ketorolac is likely to reduce the frequency of post-ERCP pancreatitis.
After a median follow-up of ~32 months, 13 of 20 responders (65%) reported clinical improvement from endotherapy/mPES.
A genetic variant was identified in 19/26 (73%) tested patients
Post-ERCP pancreatitis (PEP) was the only observed adverse event; 21% (12/58)
The authors note that the beneficial finding of improvement after mPES in children is contrary to findings in adults. In addition, there is an active sham-controlled randomized clinical trial ongoing in adults (NCT03609944). They speculate that this could be related to longer disease burden in adults. In addition, they note that their findings had limitations:
this was a retrospective study with a small sample size
the results were based on a subjective non-validated questionnaire with concerns for recall bias
My take: I am not convinced that sphincterotomy is beneficial in most children with pancreatitis and pancreas divisum –the majority of whom have an underlying genetic variant which likely triggers pancreatitis. The only way to answer this question definitely is to perform a randomized clinical trial similar to the sham-controlled study in adults.
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Patients with CP are at risk for macro- and micronutrient deficiencies. Patients should be monitored for growth and pubertal devolvement, dietary intake, and fat-soluble vitamin deficiencies. Growth and dietary intake should be reviewed at every clinic visit, a minimum of every 6 to 12 months. Fat-soluble vitamin laboratory analysis should occur every 12 to 18 months or as clinically indicated. (Grade 1B)
There is a clear role for PERT in children with CP who have EPI with steatorrhea, poor growth and/or nutritional deficiencies. PERT dosing for CP associated EPI (see Table 1) is similar to that used in patients with CF. (Grade 1B). EPI screening can be done with stool elastase (Figure 1).
Screen yearly with HbA1c level (GRADE 1C). OGTT should be performed annually once a patient is considered to have pre-diabetes. (GRADE 1C)
Insufficient data exists to recommend the use of antioxidants as a treatment to prevent EPI or other disease progression in children with CP. (GRADE 2C)
There is insufficient data to recommend PERT as therapy for pain in children without EPI. (GRADE 1B); there is insufficient data to recommend antioxidants, steroids, leukotriene antagonists, or somatostatins in the management of pain for children with CP. (GRADE 2C)
Recommends advising patients to avoid alcohol abuse and smoking
The majority of pancreatic fluid collections will resolve spontaneously with supportive care. Intervention is reserved for complications from mass-effect, infection/necrosis or if spontaneous regression of the collection is thought to be unlikely. (GRADE 1B)
This articles serves as a good review of exocrine pancreatic insufficiency (EPI).
“Cystic fibrosis is the most common cause of EPI in children .” Other congenital causes include aberrant embryonic development of the pancreas, “Shwachman-Diamond syndrome, Johanson-Blizzard syndrome, Pearson marrow pancreas syndrome, and Jeune syndrome”
“Acquired causes of EPI can be transient, such as in the aftermath of acute pancreatitis (which can persist weeks to months)”
Also, infants, compared to adults, have “physiological” EPI. Lipase output is 5–10% of adult values during the 1st 6 months of life.
Advantages/Disadvantages of Endoscopic Testing for EPI:
• Safe, technically easy, and quick procedure to perform in conjunction to routine investigative EGD
• Allows assessment of acinar and ductal function
• High sensitivity and specificity in detection of isolated and generalized enzyme deficiencies
• Can diagnose minor and more severe degrees of EPI and aid in early diagnosis of CP in patients with unremarkable radiological changes
• Can be done only in conjunction with EGD and the patient will likely require sedation• Prolongs routine EGD
• Assesses peak enzyme activity and bicarbonate concentrations rather than total secretory capacity
• No standardized pancreatic fluid collection frequency or duration in pediatrics
• Lack of age-specific standardized reference ranges in pediatrics
Endoscopic Testing Caveats:
Any sample with a pH less than 7 may be unreliable as it is below the pH optimum of the enzymes and may reflect contamination with gastric fluid; however, ” the inability to increase pH, or bicarbonate, upon secretin stimulation may be reflective of loss of cystic fibrosis transmembrane conductance regulator (CFTR) function”
My take: With careful clinical judgement, endoscopic EPI testing is rarely needed. First of all, fecal elastase measurements can detect most patients with EPI. In addition, a lot of patients with poor growth and suspected malabsorption are too young for reliable endoscopic EPI testing.